R01AI177135

The Bring BPAL2ME Trial - Comparing Nurse-Led RR-TB Treatment in Primary Care to Physician-Led, Hospital-Based RR-TB Treatment: A Cluster Randomized, Non-Inferiority Trial - In South Africa (SA), Mycobacterium tuberculosis (TB) is managed within primary care clinics (PCCs), where nurses treat drug-susceptible TB and TB/HIV coinfection with treatment outcomes rivaling the best in the world.

A PCC management strategy offers a more convenient, patient-centered, differentiated model of care that integrates TB and HIV treatment within the same setting. A diagnosis of rifampicin-resistant TB (RR-TB), however, upends this model, requiring referral to a hospital-based, physician-led outpatient treatment center.

Hospital-based, physician-led models add significant patient-associated costs, with estimates suggesting 81% of RR-TB patients experience catastrophic costs even in a decentralized outpatient model. There is hope, however, to move RR-TB care into PCCs and in many settings this involves nurse-led management.

The BringBPAL2ME Trial is a multi-principal investigator, multi-site, cluster randomized, non-inferiority trial (CR-NIT), to compare nurse-led RR-TB treatment in PCCs to standard of care physician-led RR-TB treatment at district hospitals in the provinces of KwaZulu-Natal (KZN), Gauteng (GP) and Eastern Cape (EC), SA. Clusters include 10 PCCs affiliated with 5 decentralized outpatient programs at RR-TB district hospitals (N=50 clusters).

We estimate the need to screen 3,800 RR-TB positive patients to enroll 2,944, or 64 RR-TB participants per PCC cluster. We estimate 60-70% will be HIV co-infected. The interclass correlation is 0.024 based on our prior CRT enrolling 3,000 patients in KZN and EC. The non-inferiority margin is set at 5% with the assumption of 90% treatment success in the physician-led arm.

Treatment will include either a 6-month RR-TB regimen (i.e., bedaquiline, pretomanid, linezolid and moxifloxacin, or BPALM) or fluoroquinolone-resistant TB (i.e., BPAL) regimen. The BringBPAL2ME primary aim is to conduct a 5-year, analyst and clinical safety review committee blinded, multi-site, CR-NIT to evaluate 1) treatment outcome; 2) safety; and 3) patient associated catastrophic costs with the following hypotheses: 1) outpatient nurse-led treatment in PCCs will be non-inferior to outpatient physician-led treatment at hospital-based outpatient sites among RR-TB patients, regardless of HIV co-infection, as determined by a successful treatment outcome [H1]; 2) the proportion of severe adverse events (SAEs) identified will not significantly differ by blinded, independent review [H2]; 3) patient associated catastrophic costs (i.e., costs 20% or more of household income) will be lower in nurse-led treatment [H3].

Our secondary aims include: 1) time to event analysis for a) RR-TB treatment initiation; b) smear/culture conversion; and, as applicable, c) HIV treatment initiation; d) HIV viral suppression; and e) AE and SAE symptom resolution; 2) characterization of provider adherence to guidelines for: a) dosing requirements; b) RR-TB dosing changes based on AE and SAE events; and c) AE and SAE adjuvant medication management strategy; 3) programmatic cost-effectiveness evaluation of PCC management.

Bring BPAL2ME has strong multi-PI collaborations with support from the national/provincial department of health teams and a rigorous design to evaluate effectiveness, safety and costs.

The Johns Hopkins University

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Baltimore, Maryland 212182608 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Required) (PA-20-183)

Amendment Since initial award the total obligations have increased 127% from $1,600,224 to $3,631,991.